The significance of this project is the development of a novel photoactivated collagen dressing with demonstrated bactericidal effects, minimal toxic effects and low susceptibility to mechanisms of microbial resistance in an effort to ultimately expand the armamentarium of antimicrobial agents for the management of wound infections. Approximately 2 million patients develop hospital-acquired (nosocomial) infections with surgical wound infections being the most common. It has been reported that 1 of every 24 (4.1%) patients who have inpatient surgery in the US develops a wound infection. These infections are substantial in terms of their impact on morbidity, mortality and resource use. As many as 100,000 deaths and staggering costs of $3.5B annually are associated with wound infections. In the US wound infections increase costs of hospitalization by more than $3,000/patient. While the conventional treatment of infections includes both focused and broad-spectrum antibiotics there has been a continuing and alarming trend of microbial resistance to these agents. This resistance is believed to occur as a result of chromosomal mutation, inductive expression of a latent chromosomal genes or exchange of genetic material via transformation, bacteriophage transduction, or plasmid conjugation. In-vitro and in-vivo experiments were successfully performed during Phase I. It was demonstrated that the light activated dressings significantly inhibits bacterial growth in-vitro, including biofilm scenarios. In addition, the effect is robust, reducing bacterial loads in-vivo in infected incision, wound abscess and pressure ulcer models. Similar results were obtained for Staphylococcus aureus, MRSA, Pseudomonas aeruginosa and Escherichia coli infections. The current proposal specifically aims to further refine the use of photoactivated antimicrobial collagen technology as a wound treatment to augment wound closure and healing, thereby reducing the incidence of acute and chronic wound infections. The studies performed will provide important preclinical results designed to optimize materials for human clinical studies and FDA approval. PUBLIC HEALTH RELEVANCE: Millions of surgical and iatrogenic wounds occur on an annual basis. Each requires appropriate management to facilitate healing, reduce the potential for infection and minimize disability and scarring. Wound infection and related complications increase the cost of care by nearly $9000 per occurrence and prolong hospital stays. At the same time, bacterial resistance to antibiotics is increasing at an alarming rate, with community acquired MRSA (Methicillin-resistant Staphylococcus aureus) prevalence approaching 50% in several communities based on wound culture data. This project aims to develop a novel strategy using a combination of visible light and redox-active chromophores to expand the armamentarium of antimicrobial agents for the management of surgical wounds.